| First Author | Lam QL | Year | 2006 |
| Journal | Eur J Immunol | Volume | 36 |
| Issue | 12 | Pages | 3118-30 |
| PubMed ID | 17125143 | Mgi Jnum | J:117089 |
| Mgi Id | MGI:3695554 | Doi | 10.1002/eji.200636602 |
| Citation | Lam QL, et al. (2006) Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells. Eur J Immunol 36(12):3118-30 |
| abstractText | Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob-R)-deficient db/db mice. However, it remains unclear whether or not leptin signaling plays a physiological role in dendritic cell (DC) development and function. In this study, we first detected Ob-R expression in murine DC. Using db/db mice at a pre-diabetic stage, we demonstrate that the total number of DC generated from bone marrow (BM) cultures is significantly lower than in WT controls. Similarly, selective blockade of leptin with a soluble mouse Ob-R chimera (Ob-R:Fc) inhibited DC generation in wild-type BM cultures. The reduced DC yield in db/db BM culture was attributed to significantly increased apoptosis, which was associated with dysregulated expression of Bcl-2 family genes. Moreover, db/db DC displayed markedly reduced expression of co-stimulatory molecules and a Th2-type cytokine profile, with a poor capacity to stimulate allogeneic T cell proliferation. Consistent with their impaired DC phenotype and function, db/db DC showed significantly down-regulated activities of the PI3K/Akt pathway as well as STAT-3 and IkappaB-alpha. In conclusion, our findings demonstrate the involvement of leptin signaling in DC survival and maturation. |
